title: Effect of Pluchea lanceolata bioactives in LPS-induced neuroinflammation in C6 rat glial cells.
abstract: Neuroinflammation plays a significant role in various chronic and acute pathological conditions of the central nervous system. In the Indian system of medicine, Pluchea lanceolata is used to treat the neurological disorders. We investigated the effect of major pentacyclic triterpene and its naturally occurring acetate derivative isolated from P. lanceolata on lipopolysaccharide (LPS)-stimulated neuroinflammatory condition associated to inflammatory cytokine production in rat astrocytoma cell line (C6). The log concentration dependence of Pluchea bioactive taraxasterol (Tx) significantly (p < 0.05) attenuates the release of pro-inflammatory cytokines, such as TNF-α, IFN-γ, and IL-6, while its in situ produced acetyl derivative, i.e., taraxasterol acetate (TxAc), did not inhibit the LPS-induced IL-6 production at lower concentration (p > 0.05). Surflex-Dock molecular modeling study was performed to simulate the binding capacity of compounds into the active site of the TNF-α (2AZ5), tumor protein P53 (2VUK), and NF-kappa-B (1RAM). The differential inhibition of cytokines by Tx and TxAc was further confirmed by high docking scores showing the high affinity to target proteins. Findings of the study demonstrated the comparatively greater role of Pluchea triterpene than its in situ produced acetate derivate in neuroinflammation-associated disorders.
authors.affiliation: Analytical Chemistry Department, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow, 226015, India.
authors.forename: Pooja
authors.initials: P
authors.lastname: Srivastava
authors.forename: Shilpa
authors.initials: S
authors.lastname: Mohanti
authors.forename: Dnyaneshwar Umrao
authors.initials: DU
authors.lastname: Bawankule
authors.forename: Feroz
authors.initials: F
authors.lastname: Khan
authors.forename: Karuna
authors.initials: K
authors.lastname: Shanker
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D019659:Asteraceae; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004660:Encephalitis / Q000139:chemically induced / Q000378:metabolism*; D007371:Interferon-gamma / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides; D062105:Molecular Docking Simulation; D016328:NF-kappa B / Q000378:metabolism; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D035261:Plant Components, Aerial; D010936:Plant Extracts / Q000737:chemistry; D051381:Rats; D013261:Sterols / Q000494:pharmacology*; D014315:Triterpenes / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D018696:Neuroprotective Agents; D010936:Plant Extracts; D013261:Sterols; D014315:Triterpenes; D014409:Tumor Necrosis Factor-alpha; D016159:Tumor Suppressor Protein p53; C092740:taraxasteryl acetate; C079988:taraxasterol; D007371:Interferon-gamma